The Molecular Imaging Program at Stanford (MIPS) is an inter-departmental program with the goal of advancing multimodality molecular imaging of living subjects with a particular focus on cancer. A renewal application (for years 6-10) for an in vivo cellular and molecular imaging center at Stanford (ICMIC@Stanford) P50 is now proposed. This proposal will allow continued momentum for the MIPS with a particular emphasis on clinical translation. Through significant continued investments by Stanford University in new research and clinical translational space, infrastructure, and new faculty recruitments, the MIPS are continuing to rapidly expand. Dr. Sam Gambhir, Professor of Radiology and Bioengineering, Director of MIPS, will continue to work closely with Dr. Christopher Contag, Associate Professor of Pediatrics, and Co-Director of the MIPS. Together, Drs. Gambhir (PI for this grant application) and Contag (Co-PI) form a unique leadership team that spans the breadth of disciplines involved in multimodality molecular imaging. The goal of the ICMIC@Stanford proposal is to develop state-of-the-art molecular imaging strategies for enabling cancer research and clinical translation for improved patient cancer management. Four research projects and four developmental projects spanning different components of molecular imaging research are the main science driving this grant. Two of the four research projects have specific clinical translational components that focus on predicting and monitoring response to non-small cell lung cancer (NSCLC) therapy using in vitro nano-diagnostics and molecular imaging with PET. One of the four research projects validates image-guided resection to improve outcomes for children with medulloblastoma. Another research project develops new strategies for enzyme-activated PET and MRI imaging agents. The research involves both physicians and scientists to better facilitate clinical translation. The ICMIC@Stanford investigators are from a variety of disciplines and expertise including Medical Oncology, Radiochemistry, Chemistry, Radiology, Microbiology &Immunology, Medical Physics, Bioengineering, Molecular Pharmacology and Mathematical Modeling. Three specialized resources including 1- Chemistry/Radiochemistry, 2- Small Animal Imaging, and 3- Imaging Quantitation and Analysis will help ensure that the ICMIC@Stanford grant functions efficiently. Finally, a structured training program with 2 post-docs funded by the ICMIC@Stanford with flexibility to train individuals at different career levels will ensure the ability to train next-generation interdisciplinary leaders in molecular imaging. The ICMIC@Stanford team is committed to cancer research and clinical translation of state-of-the-art molecular imaging strategies for improving clinical cancer management.